REAL-WORLD EFFICACY AND SAFETY OF DUAL ANTIPLATELET THERAPY WITH TICAGRELOR AS COMPARED TO CLOPIDOGREL

Abstract

BACKGROUND DAPT with ASA and a P2Y12 inhibitor has become a mainstay of therapy in ACS. Although ticagrelor was demonstrated to be superior to clopidogrel in the PLATO trial, North American patients did not demonstrate mortality benefit. A recent observational study of 13,897 patients from Alberta who had undergone PCI for ACS revealed that there was no difference in mortality or incidence of MACE between patients prescribed ticagrelor compared to clopidogrel when adjusted for age and comorbidities, but there was an increase in major bleeding in patients receiving ticagrelor. It is important to evaluate the efficacy of these P2Y12 inhibitors in the real-world setting. METHODS AND RESULTS We conducted a retrospective cohort study of all patients who were diagnosed with ACS and underwent PCI in a single Canadian province from January 1, 2015 to December 31, 2017. Baseline characteristics including comorbidities, medications, and bleeding risk were obtained. Propensity matching and stabilized inverse probability treatment weighting (IPTW) were used to compare patients who received ticagrelor as opposed to clopidogrel. The primary outcome was occurrence of MACE at 12 months, defined as death, nonfatal MI, or unplanned revascularization. Secondary outcomes included all-cause mortality, major bleeding, stroke, and any-cause hospitalization. A total of 3575 patients who underwent PCI for ACS were included. 1380 received clopidogrel and 2195 received ticagrelor. Patients who received clopidogrel were older and significantly more likely to have comorbidities including hypertension, COPD, peripheral vascular disease, CKD, previous ACS, previous bleeding, and HAS-BLED score 2. In 1229 propensity-score-matched pairs, there were no differences between patients given ticagrelor compared to clopidogrel in MACE (HR 0.91; 0.74-1.12 p=0.39), all-cause mortality (HR 1.00; 0.62-1.62, p=1.00), major bleeding (HR 0.85;0.44-1.64 p=0.62), or stroke (HR 0.50; 0.15-1.66, p=0.256). There was a statistically significant reduction in hospitalizations among patients treated with ticagrelor (HR 0.86; 0.71-0.99, p < 0.01). The stabilized IPTW analysis showed comparable results. CONCLUSION In a contemporary real-world cohort of ACS patients managed with PCI, ticagrelor use is associated with reduced hospitalization, but no MACE or mortality benefit in 12 months from their index PCI. These results suggest that a personalized approach to DAPT, taking into account comorbidities, ischemic, and bleeding risk may be preferable to routine use of ticagrelor in ACS patients. Analyzing data from a larger ACS patient cohort treated with PCI may help identify patient subgroups that may benefit most from use of ticagrelor as the P2Y12 inhibitor of choice. DAPT with ASA and a P2Y12 inhibitor has become a mainstay of therapy in ACS. Although ticagrelor was demonstrated to be superior to clopidogrel in the PLATO trial, North American patients did not demonstrate mortality benefit. A recent observational study of 13,897 patients from Alberta who had undergone PCI for ACS revealed that there was no difference in mortality or incidence of MACE between patients prescribed ticagrelor compared to clopidogrel when adjusted for age and comorbidities, but there was an increase in major bleeding in patients receiving ticagrelor. It is important to evaluate the efficacy of these P2Y12 inhibitors in the real-world setting. We conducted a retrospective cohort study of all patients who were diagnosed with ACS and underwent PCI in a single Canadian province from January 1, 2015 to December 31, 2017. Baseline characteristics including comorbidities, medications, and bleeding risk were obtained. Propensity matching and stabilized inverse probability treatment weighting (IPTW) were used to compare patients who received ticagrelor as opposed to clopidogrel. The primary outcome was occurrence of MACE at 12 months, defined as death, nonfatal MI, or unplanned revascularization. Secondary outcomes included all-cause mortality, major bleeding, stroke, and any-cause hospitalization. A total of 3575 patients who underwent PCI for ACS were included. 1380 received clopidogrel and 2195 received ticagrelor. Patients who received clopidogrel were older and significantly more likely to have comorbidities including hypertension, COPD, peripheral vascular disease, CKD, previous ACS, previous bleeding, and HAS-BLED score 2. In 1229 propensity-score-matched pairs, there were no differences between patients given ticagrelor compared to clopidogrel in MACE (HR 0.91; 0.74-1.12 p=0.39), all-cause mortality (HR 1.00; 0.62-1.62, p=1.00), major bleeding (HR 0.85;0.44-1.64 p=0.62), or stroke (HR 0.50; 0.15-1.66, p=0.256). There was a statistically significant reduction in hospitalizations among patients treated with ticagrelor (HR 0.86; 0.71-0.99, p < 0.01). The stabilized IPTW analysis showed comparable results. In a contemporary real-world cohort of ACS patients managed with PCI, ticagrelor use is associated with reduced hospitalization, but no MACE or mortality benefit in 12 months from their index PCI. These results suggest that a personalized approach to DAPT, taking into account comorbidities, ischemic, and bleeding risk may be preferable to routine use of ticagrelor in ACS patients. Analyzing data from a larger ACS patient cohort treated with PCI may help identify patient subgroups that may benefit most from use of ticagrelor as the P2Y12 inhibitor of choice.